Modified coronavirus spike antigen protein and uses thereof

Abstract

There is a modified coronavirus spike antigen protein and uses therefor. The spike antigen protein of coronavirus exhibits suppression of cell membrane fusion ability and improves safety by modifying two protein cleavage sites present in the coronavirus spike protein. In addition, inoculation with a vaccine having the antigen protein induces production of a large number of neutralizing antibodies to inhibit invasion of coronavirus into cells, thereby suppressing viral proliferation.

1 . A spike antigen protein of coronavirus, in which a host protease cleavage site of the spike protein of coronavirus is modified. 
     
     
         2 . The spike antigen protein of  claim 1 , wherein the cleavage site is at least one selected from the cleavage sites of the furin protease in the sequences of the S1 and S2 domains of the spike protein of coronavirus and the cleavage site of the protease in the S2′ sequence thereof. 
     
     
         3 . The spike antigen protein of  claim 1 , wherein the coronavirus is at least one selected from the group consisting of severe acute respiratory syndrome coronavirus1 (SARS-CoV), severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and variants thereof. 
     
     
         4 . The spike antigen protein of  claim 2 , wherein the coronavirus is SARS-CoV-2, the furin protease cleavage site is at amino acid 685 of the spike protein, and the protease cleavage site in the S2′ sequence is at amino acid 815 of the spike protein. 
     
     
         5 . The spike antigen protein of  claim 4 , wherein amino acid 685 at the furin protease cleavage site is substituted with at least one amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, threonine, serine, cysteine, methionine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, histidine, phenylalanine, tyrosine, tryptophan, and proline. 
     
     
         6 . The spike antigen protein of  claim 4 , wherein, at the cleavage site of the protease in the S2′ sequence, amino acid 815 of the spike protein is substituted with at least one amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, threonine, serine, cysteine, methionine, aspartic acid, asparagine, glutamic acid, glutamine, phenylalanine, tyrosine, tryptophan, and proline. 
     
     
         7 . The spike antigen protein of  claim 1 , wherein the modified spike antigen protein of coronavirus inhibits the generation of a free S1 domain. 
     
     
         8 . The spike antigen protein of  claim 1 , wherein the modified spike antigen protein of coronavirus inhibits cell membrane fusion. 
     
     
         9 . The spike antigen protein of  claim 1 , wherein the modified spike antigen protein of coronavirus inhibits intracellular entry of the virus or intracellular transfer of the viral genome. 
     
     
         10 . A recombinant vector for expressing an antigen protein of coronavirus, comprising a gene encoding the spike antigen protein of coronavirus of  claim 1 . 
     
     
         11 - 17 . (canceled) 
     
     
         18 . A method of preventing or treating coronavirus infection, comprising administering the spike antigen protein of coronavirus of  claim 1  to an individual in need thereof.